In the recently issued U.S. Pat. No. 3,843,682 there is disclosed a process for preparing 3-methyl-2-(2-chlorosulfinyl-4-oxo-3-imido-1-azetidinyl)-3-butenoate esters, variously termed "2-chlorosulfinyl-3-imido-azetidin-4-ones". These compounds are prepared from the corresponding penicillin sulfoxide esters by reaction of the latter with sulfuryl chloride at a temperature of from about 75.degree. C. to about 120.degree. C. The compounds which are prepared by this known process are exclusively the 3-imido substituted 2-chlorosulfinylazetidin-4-ones since the process is limited to the use of the 6-imido penicillin sulfoxide esters as starting material. There is no disclosure of the use of or the possibility to use what would be preferred and more readily available, that is, the 6-amido penicillin sulfoxide esters, including the conveniently obtainable penicillin sulfoxide derivatives of the naturally occurring Penicillin G and/or Penicillin V. When one attempts to carry out the reaction disclosed in U.S. Pat. No. 3,843,682 using a 6-amido penicillin sulfoxide ester as starting material, the product which is obtained is a complex mixture containing no 2-chlorosulfinylazetidin-4-one product, or, at most, the latter in a quantity so minute as to be undetectable by ordinary analytical techniques. Therefore, this previously disclosed method, since it requires the absence of an amide hydrogen in the 6-position of the penicillin sulfoxide starting material, has inherent and significant drawbacks since it requires, first, displacement of the naturally occurring 6-substituent of a penicillin by an imido substituent, and, secondly, cleavage of the imido substituent in order to permit reacylation to introduce the substituent of the intended final antibiotic product. It now has been discovered that it is possible to prepare sulfinyl chloride intermediates from 6-amido penicillin sulfoxide esters by altering the conditions of reaction as well as the halogenating agent which is employed. This thereby avoids the previously recognized necessity to block the amide hydrogen in the 6-position of the penicillin sulfoxide starting material by conversion to an amide derivative. It is to such a process as well as to hitherto unavailable compounds produced therefrom that this invention is directed.
The 2-chlorosulfinylazetidin-4-ones produced by the process of this invention can be ring closed to produce a 3-exomethylenecephem sulfoxide ester. Cyclization of the 2-chlorosulfinylazetidin-4-ones to their corresponding 3-exomethylenecepham sulfoxides is accomplished by a FriedelCrafts catalyst induced intramolecular reaction involving the sulfinyl chloride and olefinic moieties of the azetidin4-one starting material.